Osmotic devices have demonstrated utility in delivering useful active agents such as medicines, nutrients, food products, pesticides, herbicides, germicides, algaecides, chemical reagents, and the like to an environment of use in a controlled manner over prolonged periods of time. Known devices include tablets, pastilles, pills or capsules and others and generally include layers comprising one or more materials that are subject to erosion or that slowly dissolve in the environment of use thereby gradually dispensing the active agent.
U.S. Pat. No. 4,014,334 to Theeuwes et al. discloses an osmotic device for the controlled and continuous delivery of a drug wherein the device comprises: a) a core containing a drug and an osmotic agent; b) a semipermeable laminate, surrounding the core, which includes an external semipermeable lamina and an internal semipermeable lamina; and c) a passageway which communicates the core with the exterior of the device. The two semipermeable laminae maintain their chemical and physical integrity in the presence of the drug and fluid from the environment. The passageway of the Theeuwes et al. Patent includes an aperture, orifice or bore through the laminate formed by mechanical procedures, or by eroding an erodible element, such as a gelatin plug, in the environment of use. The Theeuwes et al. Patent does not disclose a third lamina containing drug or a polymer coat comprising poly(vinylpyrrolidone)-(vinyl acetate) copolymer surrounding the semipermeable membrane.
U.S. Pat. No. 4,576,604 to Guittard et al. (the "Guittard et al. '604") corresponds to Argentina Patent No. 234,493 and discloses several different embodiments of an osmotic device having a drug in the core and at least one lamina surrounding the core. Specifically, one embodiment of the osmotic device comprises: a) a core containing a drug formulation which can include an osmotic agent for controlled release of the drug; b) a semipermeable wall comprising an inner semipermeable lamina, a middle microporous lamina, and an outer water soluble lamina containing drug; and c) a passageway which communicates the core with the exterior of the device. The Guittard et al. '604 Patent does not disclose the use of poly(vinylpyrrolidone)-(vinyl acetate) copolymer as a material suitable for the microporous lamina or the erodible element.
U.S. Pat. No. 4,673,405 to Guittard et al. (the "Guittard et al. '405 Patent") discloses an osmotic device comprising: a) a core, or compartment, containing a beneficial agent; b) an inert semipermeable wall containing a beneficial agent surrounding the core; and c) at least one passageway in the wall of the osmotic device which is formed when the osmotic device is in the fluid environment of use and the fluid contacts and thus releases the beneficial agent in the wall, wherein the formed passageway communicates with the compartment in the osmotic device and the exterior of the device for dispersing the beneficial agent from the compartment when the device is in the fluid environment of use. The Guittard et al. '405 Patent discloses the use of an erodible element to form the passageway; however, it does not disclose the use of poly(vinylpyrrolidone)-(vinyl acetate) copolymer as a material suitable for the erodible element.
U.S. Pat. No. 5,558,879 to Chen et al. (the "Chen et al. '879 Patent") discloses a controlled release tablet for water soluble drugs in which a passageway is formed in the environment of use, i.e., the GI tract of a person receiving the formulation. Specifically, the controlled release tablet consists essentially of: a) a core containing a drug, 5-20% by weight of a water soluble osmotic agent, a water soluble polymer binder and a pharmaceutical carrier; and b) a dual layer membrane coating around the core consisting essentially of: (1) an inner sustained release coating containing a plasticized water insoluble polymer and a water soluble polymer; and (2) an outer immediate release coating containing a drug and a water soluble polymer. Although, the Chen et al '879 Patent discloses the formation of a passageway in a controlled release tablet in an environment of use to form an osmotic tablet, the passageway is not formed by employing an erodible element comprising poly(vinylpyrrolidone)-(vinyl acetate) copolymer which covers a pre-formed aperture.
U.S. Pat. No. 4,810,502 to Ayer et al. (the "Ayer et al. '502 Patent") discloses an osmotic dosage form for delivering pseudoephedrine (Ps) and brompheniramine (Br) which comprises: a) a core containing Ps and Br; b) a wall surrounding the core comprising cellulose acylate and hydroxypropylcellulose; c) a passageway in the wall for delivering the drug; and d) a lamina on the outside of the wall comprising Ps, Br, at least one of hydroxypropylcellulose and hydroxypropyl methylcellulose, and poly(ethylene oxide) for enhancing the mechanical integrity and pharmacokinetics of the wall. The Ayer et al '502 Patent does not disclose a polymer coat between the wall and the drug-containing lamina as required by the present invention.
U.S. Pat. No. 4,801,461 to Hamel et al. (the "Hamel et al. '461 Patent") discloses an osmotic dosage form for delivering pseudoephedrine (Ps). Specifically, the osmotic dosage form comprises: a) a core containing varying amounts of Ps; b) a semipermeable wall surrounding the core comprising varying amounts of cellulose acetate or cellulose triacetate and varying amounts of hydroxypropylcellulose; c) a passageway in the wall for delivering the drug from the core; and optionally d) a lamina on the outside of the wall comprising Ps. The core can also contain one or more of sodium chloride, microcrystalline cellulose, hydroxypropyl methylcellulose, magnesium stearate, and poly(vinylpyrrolidone). The passageway of this device can extend through the semipermeable wall alone or through both the semipermeable wall and the outer lamina. The passageway also includes materials that erode or leach in the environment of use. Although a variety of erodible materials are listed as suitable for use in forming the passageway, the specification does not disclose or suggest poly(vinylpyrrolidone)-(vinyl acetate) copolymer for this use. Further, the Hamel et al. 461 Patent does not contemplate a polymer coat positioned between the drug-containing outer lamina and the semipermeable wall.
U.S. Pat. No. 5,681,584 to Savastano et al. (the "Savastano et al. '584 Patent") discloses a controlled release drug delivery device comprising: a) a core containing a drug, an optional osmotic agent and optional excipients; b) a delayed release jacket comprising at least one of a binder, an osmotic agent and a lubricant surrounding the core; c) a semipermeable membrane surrounding the delayed release jacket and optionally having a passageway; d) a drug-containing layer either on the outside of the semipermeable membrane or between the semipermeable membrane and the delayed release jacket; and e) an optional enteric coat either on the outside of the drug-containing layer, between the drug-containing layer and the semipermeable membrane or on the outside of the semipermeable membrane when the drug-containing layer is between the delayed release jacket and the semipermeable membrane. Thus, the device of the Savastano et al. '584 Patent requires a delayed release jacket and does not include a water soluble poly(vinylpyrrolidone)-(vinyl acetate) copolymer polymer coat between the semipermeable membrane and the drug-containing layer.
Additional exemplary osmotic devices for the controlled delivery of active agents are described in U.S. Pat. No. 3,845,770 and Argentina Patent No. 199,301 which disclose an osmotic device formed by a wall that surrounds a compartment housing agent. The wall has a passageway or orifice that links the compartment to the environment of use. The wall is made of semipermeable material which is semipermeable to an external fluid and impermeable to an active agent within the device. Neither of these patents disclose a water soluble poly(vinylpyrrolidone)-(vinyl acetate) copolymer polymer coat between the semipermeable membrane and the drug-containing layer.
While the prior art discloses a wide variety of multi-layered osmotic devices, no single device has been found to be generally applicable and, in fact, most known devices are designed to operate within a relatively narrow range of conditions in an environment of use. It has now been discovered that the improved multi-layered osmotic device disclosed herein overcomes many of the disadvantages inherent in related prior art devices. The present osmotic device is capable of providing a broader range of independent release profiles for one or more active agents either simultaneously or sequentially due to the particular improvements disclosed herein. Further, the present osmotic device provides greater control over the release of active agent from the layers versus the core of the device.